Disrupting Alzheimer’s Disease Research

Challenge Program Aims at Avoiding Impending Epidemic for Aging Population

Women are disproportionately affected by Alzheimer’s disease. In fact, two-thirds of AD patients in the United States are women. [Sandor Kacso/fotolia.com]

The 2013 Geoffrey Beene Global Neuro Discovery Challenge* on male/female differences in the presymptomatic, early symptomatic, and late dementia stages of Alzheimer’s Disease (AD), with $100,000 in prize awards, attempts to leverage large sets of clinical data and novel analytical approaches.

The challenge is seeking to encourage multidisciplinary teams to analyze public datasets from the National Institute on Aging and other research centers for differences between men and women in cognition, biomarkers, and progressive neurodegenerative decline due to AD.

Women are disproportionally affected by AD; two-thirds of AD patients in the U.S. States are women. This disparity may be due in part to women’s longer life spans, but recent research in mild cognitive impairment is beginning to point toward differences between men and women in the pathology and progression of this disease. Anatomical, molecular, functional, hormonal, and cognitive differences in the brain between males and females have been reported in many species, including humans.

What biological sex differences in the brain mean for impairments in memory and progressive neurodegenerative diseases such as AD is not known. However, studies are accumulating that show a distinct male/female difference in the onset, course, and presentation of AD.

For example, one study reported that women had more neurofibrillary tangles. Increased AD pathology was associated with a nearly 3-fold increase of clinical AD in men, compared with a more than 20-fold increase in women. These and other data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women.

In the Alzheimer’s Disease Neuroimaging Initiative (ADNI), patients were grouped into three clinical categories (probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls). Men and women in the AD and aMCI groups showed different patterns of decline through time. In another ADNI study of brain atrophy rates, statistical mapping revealed significant age and sex differences, with rates of brain atrophy being about 1.0–1.5% faster in women than in men.

The Mayo Clinic Study of Aging reported that incidence rates for MCI were higher in men than women and suggested that risk factors for MCI should be investigated separately in men and women.

Also, the Australian Imaging Biomarker Lifestyle study of aging reported gender differences in β-amyloid levels, which was associated with worse episodic memory and visuospatial performance in females than in males.

Genetic Studies

Genetic studies are also revealing AD differences between women and men. Female carriers of ApoE4, a strong AD risk factor, have significantly more AD brain atrophy and memory disruption than men and rates of atrophy are faster. Additionally, differential risk for AD was associated with estrogen receptor ERα and ERβ genotypes. Studies have reported evidence for greater inheritance of AD from the maternal lineage.

The 2013 Geoffrey Beene NeuroDiscovery Challenge seeks to foster a disruptive approach to Alzheimer’s by looking through the lens of male/female differences. We anticipate that any successful solution to the Challenge will be composed of two parts:

A clearly articulated novel hypothesis related to the causes or consequences of male/female differences (molecular, physiological, anatomical, hormonal, cognitive, genetic, etc.) in the pathogenesis and presentation of AD in its presymptomatic, early symptomatic, and late stages. The hypothesis needs to be accompanied by a solid scientific rationale and supported by analysis of data obtained separately for women and men.

A detailed research plan describing how to test the proposed hypothesis.

The Geoffrey Beene Foundation Alzheimer’s Initiative envisions that up to five awards, with no single award being lower than $10,000, will be awarded to proposals that best meet the requirements of the challenge. Solutions will be evaluated by a panel of expert judges for their innovation and originality, the biological and clinical rationale for the hypothesis, and the technical rigor of the analyses or experimental design.

One solution will be awarded an additional $50,000 to support additional database analysis or the proposed research plan.

Understanding and characterizing these biological sex-based variations, and others yet to be discovered, will provide new opportunities for the development of appropriate, tailored disease detection, treatment, and prevention modalities for both men and women.

Matching a research challenge with an advocacy agenda both informs the science and energizes the mobilization of women against Alzheimer’s. Challenging researchers to use existing big data as well as develop new methodologies to investigate any sex-based differences that may exist could ultimately affect how we treat—and, hopefully, one day prevent—this devastating disease.

*The 2013 Geoffrey Beene Global Neuro Discovery Challenge generated over 800 open project rooms from 65 countries resulting in over 80 qualified submissions from 23 countries. The winner will be selected from combined online/live voting that will run November 1–5. To learn more about the Foundation and to cast your vote, please visit www.geoffreybeenechallenge.org.

Meryl Comer is president of the Geoffrey Beene Foundation Alzheimer’s Initiative, Maria C. Freire is president of The Foundation for the National Institutes of Health, and Alan J. Russell, Ph.D., is Highmark Distinguished Career Professor at Carnegie Melon University. This article is adapted from Disruptive Science and Technology, Vol. 1, No. 4, 2012/2013, published by Mary Ann Liebert, Inc.

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